African Americans share a disproportionate burden of lung cancer incidence and mortality; Mexican Americans exhibit substantially lower rates. These racial differences may represent interactions of environmental and genetic influences. This multidisciplinary study of genetic susceptibility to lung cancer in African Americans and Mexican Americans will incorporate and integrate epidemiologic, cytogenetic, molecular, and socio-psychological data. A case control study of 100 black African American and 100 Mexican American patients with previously untreated lung cancer, ascertained from The University of Texas M.D. Anderson Cancer Center, St. Joseph Hospital, Hermann Hospital and Lyndon Baines Johnson Hospital is planned. Two hundred (200) controls from each ethnic group, selected from local community centers will be age- and sex-frequency matched to the cases. Environmental exposures, family history, dietary intake, and socio-psychological factors will be ascertained by personal interview. Primary chromosome changes and bleomycin-induced chromosome breaks in lymphocyte cultures of cases and controls, and in lung tissue of cases will be assessed and the role of confounding with carcinogenic exposures will be examined. The molecular component will focus on p53 alterations in lung cancer tissue, dysplastic bronchial epithelia and peripheral lymphocytes of cases, and in peripheral lymphocytes of controls identified as current smokers. The sociodemographic component will focus on inter and intra-ethnic differences in perceived risk of disease. Since lung cancer is the leading cause of cancer mortality, the identification of genetic markers of risk has great potential for cancer control. The use of genetic markers of risk enhances the power of this multidisciplinary epidemiologic research project.